Prostate CancerPhase 1NCT02182622
LDE225 + Docetaxel/Prednisone for Adv/Met Castrate Resistant Prostate Cancer w/ Disease Progression After Docetaxel
A Phase 1 study testing Docetaxel, Prednisone and LDE225 in people with Prostate Cancer, run by Martin Gutierrez at 1 site in United States.
Trial summary
The purpose of this study is to first determine the highest dose of LDE225 combined wtih Docetaxel and Prednisone that can be given that does not cause unacceptable side effects when given to patients with castrate resistant prostate cancer who failed previous docetaxel therapy. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Docetaxel, Prednisone and LDE225
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male patients 18 years or older
- Histologically documented prostate adenocarcinoma with progressive systemic (clinically metastatic disease as documented in bone, CT or MRI scans) disease despite castrate levels of testosterone due to orchiectomy or Luteinizing-hormone-releasing hormone (LHRH) antagonist
- Must have received prior Docetaxel treatment with evidence of disease progression AND have at least one (e.g. Abiraterone Acetate, Enzalutamide, Cabazitaxel, Radium-223) of the four FDA approved therapies
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors) or other specific response assessment criteria as appropriate
- Able to swallow and retain oral medication
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- Must have a castrate level of testosterone (=/< 50ng/dl or 1.7nmol/L). Castrate status must be maintained by continued gonadotropin-releasing hormone (GnRH) analogues unless patient has undergone surgical orchiectomy
- Discontinuation of all anti-androgen (except GnRH analogues - patients will continue on GnRH analogues to maintain castrate levels during study), anti-neoplastic or investigational treatment =/> 4 weeks (6 weeks for bicalutamide)
- Must have documented progressive disease to the previous line of therapy according to the Prostate Cancer Working Group 2 (PCWG2) criteria: patients who progressed based solely on Prostate Specific Antigen (PSA) rising, should have had a sequence of rising values on 3 consecutive occasions of at least 1 week intervals and should have 5.0ng/mL minimum level for entry; patients who manifested disease progression per the Response Evaluation Criteria in Solid Tumors (RECIST) are eligible independent of PSA; patients who manifest with bone only progressive disease, according to PCWG2 are eligible.
- Absolute Neutrophil Count (ANC) ≥ 1.5 x 10^9/L
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥ 80 x 10^9/L
- Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate Aminotransferate (AST) and Alanine Transaminase (ALT) ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present
- Plasma creatine phosphokinase (CK) < 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50ml/min
Who cannot join
- Asymptomatic or minimally symptomatic patients with docetaxel naïve metastatic castration resistant prostate cancer
- Patients who have had major surgery within 4 weeks of initiation of study medication
- Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data
- Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract or known malabsorption syndromes (e.g., ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- Patients who have previously been treated with systemic LDE225 or with other Hh pathway inhibitors
- Patients who have active uncontrolled or symptomatic central nervous system (CNS) metastases
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- History of hypersensitivity to LDE225 or to drugs of similar chemical classes
- Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting LDE225 treatment. If it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution
- Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on LDE225 treatment
- Patients who have taken part in an experimental drug study within 4 weeks or 5 half-lives, whichever is longer, of initiating treatment with LDE225
- Patients who are receiving other anti-neoplastic therapy besides Docetaxel (e.g. chemotherapy, targeted therapy or radiotherapy) concurrently or within 2 weeks of starting treatment with LDE225
- Patients who are receiving treatment with medications known to be moderate and strong inhibitors or inducers of Cytochrome P450 3A4/5 (CYP3A4/5) or drugs metabolized by Cytochrome P450 2B6 (CYP2B6) or Cytochrome P450 2C9 (CYP2C9) that have narrow therapeutic index, and that cannot be discontinued before starting treatment with LDE225. Medications that are strong CYP3A4/5 inhibitors should be discontinued at least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting treatment with LDE225
- Patients who require the use of warfarin (substrate of CYP2C9) cannot be enrolled as LDE225 is a competitive inhibitor of CYP2C9 based on in-vitro data
- Impaired cardiac function or clinically significant heart disease, including any one of the following: Angina pectoris within 3 months Acute myocardial infarction within 3 months QTcF > 450 msec for males and > 470 msec for females on the screening ECG A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
- Prior to study entry any ECG abnormality has to be documented by the investigator as not medically relevant
Trial locations and contacts
1 site in 1 country.
United States1 site
John Theurer Cancer @ HackensackUMC
Hackensack, New Jersey, 07601
About this study
Official title: Ib Dose Finding Study of LDE225 Plus Docetaxel/Prednisone in Patients With Advanced or Metastatic Castration Resistant Prostate Cancer Who Experience Disease Progression After Receiving Docetaxel
The purpose of this study is to first determine the highest dose of LDE225 combined wtih Docetaxel and Prednisone that can be given that does not cause unacceptable side effects when given to patients with castrate resistant prostate cancer who failed previous docetaxel therapy.
- Conditions
- Prostate Cancer
- Being tested
- Docetaxel, Prednisone, LDE225
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
PrednisoneDrug
LDE225Drug
| Study group | Role | What they receive |
|---|---|---|
| Dose Level -1 | Experimental | Docetaxel 60mg/m2 IV every 21 days Prednisone 5mg oral twice daily LDE225 200mg oral daily Receives: Drug: Docetaxel; Drug: Prednisone; Drug: LDE225 |
| Dose Level 1 | Experimental | Docetaxel 75mg/m2 IV every 21 days Prednisone 5mg oral twice a day LDE225 200mg oral daily Receives: Drug: Docetaxel; Drug: Prednisone; Drug: LDE225 |
| Dose Level 2 | Experimental | Docetaxel 75mg/m2 IV every 21 days Prednisone 5mg oral twice daily LDE225 400mg oral daily Receives: Drug: Docetaxel; Drug: Prednisone; Drug: LDE225 |
| Dose Level 3 | Experimental | Docetaxel 75mg/m2 IV every 21 days Prednisone 5mg oral twice daily LDE225 800mg oral daily Receives: Drug: Docetaxel; Drug: Prednisone; Drug: LDE225 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
Measured: From date of first dose until documentation of unacceptable toxicity or documented disease progression, whichever came first, assessed at up to days 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionDec 2015 (estimated)
- Study completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Martin Gutierrez
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor-investigator, Martin Gutierrez, Hackensack Meridian Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02182622
- Sponsor's protocol ID
- IST-LDE225
- Status last verified
- Jun 2019
- First submitted
- 27 Jun 2014
- Last updated
- 19 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ib Dose Finding Study of LDE225 Plus Docetaxel/Prednisone in Patients With Advanced or Metastatic Castration Resistant Prostate Cancer Who Experience Disease Progression After Receiving Docetaxel
- ClinicalTrials.gov ID
- NCT02182622
- Acronym / sponsor ID
- IST-LDE225
- Conditions
- Prostate Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Martin GutierrezUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jul 2014
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 8 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to first determine the highest dose of LDE225 combined wtih Docetaxel and Prednisone that can be given that does not cause unacceptable side effects when given to patients with castrate resistant prostate cancer who failed previous docetaxel therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Level -1 | Experimental | Drug: Docetaxel, Drug: Prednisone, Drug: LDE225Docetaxel 60mg/m2 IV every 21 days Prednisone 5mg oral twice daily LDE225 200mg oral daily |
| Dose Level 1 | Experimental | Drug: Docetaxel, Drug: Prednisone, Drug: LDE225Docetaxel 75mg/m2 IV every 21 days Prednisone 5mg oral twice a day LDE225 200mg oral daily |
| Dose Level 2 | Experimental | Drug: Docetaxel, Drug: Prednisone, Drug: LDE225Docetaxel 75mg/m2 IV every 21 days Prednisone 5mg oral twice daily LDE225 400mg oral daily |
| Dose Level 3 | Experimental | Drug: Docetaxel, Drug: Prednisone, Drug: LDE225Docetaxel 75mg/m2 IV every 21 days Prednisone 5mg oral twice daily LDE225 800mg oral daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Male patients 18 years or older
- Histologically documented prostate adenocarcinoma with progressive systemic (clinically metastatic disease as documented in bone, CT or MRI scans) disease despite castrate levels of testosterone due to orchiectomy or Luteinizing-hormone-releasing hormone (LHRH) antagonist
- Must have received prior Docetaxel treatment with evidence of disease progression AND have at least one (e.g. Abiraterone Acetate, Enzalutamide, Cabazitaxel, Radium-223) of the four FDA approved therapies
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors) or other specific response assessment criteria as appropriate
Key exclusion criteria (15 listed)
- Asymptomatic or minimally symptomatic patients with docetaxel naïve metastatic castration resistant prostate cancer
- Patients who have had major surgery within 4 weeks of initiation of study medication
- Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data
- Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract or known malabsorption syndromes (e.g., ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- Patients who have previously been treated with systemic LDE225 or with other Hh pathway inhibitors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Docetaxel | Drug | Dose Level -1, Dose Level 1, Dose Level 2, Dose Level 3 |
| Prednisone | Drug | Dose Level -1, Dose Level 1, Dose Level 2, Dose Level 3 |
| LDE225 | Drug | Dose Level -1, Dose Level 1, Dose Level 2, Dose Level 3 |
Primary outcome
Maximum Tolerated Dose
Time frame: From date of first dose until documentation of unacceptable toxicity or documented disease progression, whichever came first, assessed at up to days 42
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Docetaxel, Prednisone and LDE225 in people with Prostate Cancer, run by Martin Gutierrez at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: From date of first dose until documentation of unacceptable toxicity or documented disease progression, whichever came first, assessed at up to days 42). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2019.